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Biomedical subjects

N Oakes

Publications and source records attributed to N Oakes.

5 recordsLinked to original sources
PubMed2001

Pharmacological treatment of insulin resistance in obesity.

AIM: To discuss new pharmacological possibilities for acting on the lipid metabolism abnormalities relating obesity, insulin resistance and arterial disease. DATA SYNTHESIS: Obesity is frequently associated with excess caloric fat dietary intake, especially in the form of fatty acids. An increased flux of fatty acids into muscle, liver and pancreas is probably a major cause of insulin resistance and possibly of pancreatic secretory disturbances. Liver exposure to fatty acid overload may also be the main reason for the atherogenic lipoprotein profile of insulin resistance and type 2 diabetes, which is characterised by prolonged post-prandial hypertriglyceridemia, high levels of large very low-density lipoproteins (VLDL) and small, dense low-density lipoproteins (LDL), and a reduced number of apoAl-containing high-density lipoproteins (HDL). This lipoprotein profile may be the main contributor to the high prevalence of arterial disease in patients with type 2 diabetes. The treatment of type 2 diabetes and insulin resistance in obese or non-obese subjects should therefore aim at normalising fatty acid fluxes because this can be expected to enhance insulin action and ameliorate the atherogenic lipoprotein abnormalities. The discovery of peroxisome proliferator-activated receptors (PPARs) and the elucidation of their function as master controllers of the genes involved in fatty acid metabolism have facilitated the development of potent modulating substances. Promising results have been obtained with the current generation of PPAR gamma ligands, but undesirable effects have also been reported. CONCLUSIONS: New knowledge concerning the structure and function of PPAR gamma and PPAR alpha is being used to develop non-TZD modulators with combined PPAR alpha and gamma actions in animal studies. This new generation of substances may offer a more balanced spectrum of activity that may be better suited for the treatment of the insulin resistance and type 2 diabetes frequently associated with obesity.

Animals↗
PubMed1992

Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias.

The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

The urgency of restraint.

INTRODUCTION: the environment in which we will be operating--ever-growing demand for services; developments in medicine. Some figures on expenditure trends. The supply side: the imperfections of the market place; whose choice? The pricing mechanism: capacity to pay: choice--again. Who pays? Fiscal accountability and responsibility.

Australia↗